TNFR Pathway-Related Proteins and Recurrent Coronary Artery Disease Events

Despite optimization with lifestyle modifications and medications, complications of coronary artery disease (CAD) remain the leading cause of adult mortality worldwide. This study aimed to identify proteins and pathways linked to recurrent CAD events to better understand residual risk. We used data from 1,009 participants in the UK Biobank (UKB) with baseline Olink plasma proteomic measures and CAD. Among 1,463 proteins tested, 102 proteins were independently associated with recurrent CAD events. Molecular functions were significantly enriched for tumor necrosis factor receptor (TNFR) activity by 100-fold (p-value = 6.37×10 ^-10 ). Of the 16 proteins related to TNF annotated by Gene Ontology, TNF-alpha, TNFR1, and TNFR2 were all significantly associated with increased risk of recurrent CAD events. While TNFR1 and TNFR2 were initially thought to have opposing roles in cardiac remodeling post-MI, this study highlights the complex interaction between these pathways and the need to identify specific inflammation-related targets to therapeutic strategies.